1. Field of the Invention
This invention generally relates to a composition comprising at least a phospholipid such as phosphoryl choline that is useful for coating an implantable device such as a drug eluting stent.
2. Description of the Background
Implanted stents have been used to carry medicinal agents, such as thrombolytic agents. U.S. Pat. No. 5,163,952 to Froix discloses a thermal-memoried expanding plastic stent device formulated to carry a medicinal agent in the material of the stent itself. Pinchuk, in U.S. Pat. No. 5,092,877, discloses a stent of a polymeric material which may have a coating associated with the delivery of drugs. Other patents which are directed to devices of the class utilizing bio-degradable or bio-absorbable polymers include Tang et al., U.S. Pat. No. 4,916,193, and MacGregor, U.S. Pat. No. 4,994,071.
A patent to Sahatjian, U.S. Pat. No. 5,304,121, discloses a coating applied to a stent consisting of a hydrogel polymer and a preselected drug such as cell growth inhibitors or heparin. A further method of making a coated intravascular stent carrying a therapeutic material is described in Berg et al., U.S. Pat. No. 5,464,650, issued on Nov. 7, 1995 and corresponding to European Patent Application No. 0 623 354 A1 published Nov. 9, 1994. In that disclosure, a polymer coating material is dissolved in a solvent and the therapeutic material dispersed in the solvent; the solvent evaporated after application.
An article by Michael N. Helmus entitled “Medical Device Design—A Systems Approach: Central Venous Catheters”, 22nd International Society for the Advancement of Material and Process Engineering Technical Conference (1990) relates to polymer/drug/membrane systems for releasing heparin. Those polymer/drug/membrane systems require two distinct types of layers to function.
It has been recognized that contacting blood with the surface of a foreign body in vivo has a tendency to induce thrombogenic responses, and that, as the surface area of a foreign device in contact with host blood increases, the tendency for coagulation and clot forming at these surfaces also increases. This has led to the use of immobilized systemic anti-coagulant or thrombolytic agents such as heparin on blood-contacting surfaces such as blood oxygenator, hemodialysis membrane devices to reduce this phenomenon. Such an approach is described by Winters, et al., in U.S. Pat. Nos. 5,182,317; 5,262,451 and 5,338,770 in which the amine functional groups of the active material are covalently bonded using polyethylene oxide (PEO) on a siloxane surface.
Another approach is described in U.S. Pat. No. 4,613,665 to Larm in which heparin is chemically covalently bound to plastic surface materials containing primary amino groups to impart a non-thrombogenic surface to the material. Other approaches for bonding heparin are described in Barbucci, et al., “Coating of commercially available materials with a new heparinizable material”, Journal of Biomedical Materials Research, Vol. 25, pp. 1259-1274 (1991); Hubbell, J. A., “Pharmacologic Modification of Materials”, Cardiovascular Pathology, Vol. 2, No. 3 (Suppl.), 121S-127S (1993); Gravlee, G. P., “Heparin-Coated Cardiopulmonary Bypass Circuits”, Journal of Cardiothoracic and Vascular Anesthesia, Vol. 8, No. 2, pp. 213-222 (1994). Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a stent. Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. To effect a controlled delivery of an active agent in stent based therapy, the stent can be coated with a biocompatible polymeric coating. The biocompatible polymeric coating can function either as a permeable layer or a carrier to allow a controlled delivery of the agent. A continuing challenge in the art of implantable stents is to provide a coating that possesses good biobeneficial properties, which refer to good biocompatibilities in both the acute and chronic timeframes.
Generally, a polymer forming a coating composition for an implantable device has to be at least biologically benign. Additionally, the polymer could have a therapeutic effect either additively or synergistically with the bioactive agent. The polymer is preferably biocompatible. To provide for a coating that is biologically benign, various compositions have been used with limited success. For example, coating compositions containing poly(ethylene glycol) have been described (see, for example, U.S. Pat. No. 6,099,562). One of the needs in the art is to provide for a coating that has favorable long term biological properties.
Phosphoryl choline (PC) has a zwitterionic functionality that mimics the outer blood-contacting surface of the lipid bilayer structure in blood corpuscles. PC possesses numerous biobeneficial properties such as hemocompatibility, non-thrombogenicity, arterial tissue acceptance and long-term in vivo stability. PC has been used to increase biocompatibility of polymers, especially that of acrylic copolymers.
The polymer and methods of making the polymer disclosed herein address the above described problems.